DESCRIPTION: The objective of this project is to use noninvasive hypoxic imaging to identify clinically and biologically radioresistant hypoxic tumors and to target them with higher radiation doses by intensity modulated radiation therapy (IMRT) to overcome hypoxic resistance. It is proposed to achieve this objective by validating the efficacy of a novel hypoxic tumor imaging method for identifying radioresistant tumors in patients with locally advanced head and neck cancers, and by understanding the geometric distribution of the hypoxic tumor subvolume, which may evolve within the gross tumor volume (GTV) during radiation treatment. Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone), or (Cu-ATSM), is a newly developed hypoxic marker for detecting tumor hypoxia noninvasively by positron emission tomography (PET). In the following two aims the applicants will test the hypothesis that Cu-60-ATSM PET can effectively image radiobiologically resistant hypoxic tumor and can help to understand its spatial distribution and displacement during therapy. Then hypoxic-image-guided conformal radiation therapy can be implemented clinically. In Specific Aim 1 the applicants will determine whether hypoxic head and neck tumors, as judged by Cu-ATSM PET scan activity, are more resistant to radiation therapy. They hypothesize that head and neck tumors with larger hypoxic tumor volume (hGTV) will have more residual disease by surgical/pathological assessment. In Specific Aim 2 the applicants will determine whether the pretreatment hypoxic tumor target volume encompasses all regions of hypoxic tumor during the course of radiation therapy. They will test the hypothesis by performing multiple Cu-60 ATSM PET scans during the course of irradiation to understand the spatial evolution of hypoxic tumor.